Therapeutic potential of aleglitazar, a new dual PPAR-α/γ agonist: implications for cardiovascular disease in patients with diabetes mellitus

American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions
Matthew A Cavender, A Michael Lincoff

Abstract

Preventing morbidity and mortality from diabetes mellitus is of paramount importance as the incidence of this disease is increasing across the world. While microvascular complications of diabetes such as nephropathy, retinopathy, and neuropathy are reduced with intensive glycemic control, treatment of hyperglycemia has not been consistently shown to have effects on the macrovascular complications of diabetes such as coronary artery, cerebrovascular, and peripheral vascular disease. Preventive efforts have accordingly shifted toward the modification of other cardiovascular risk factors in diabetic patients. Agonism of the peroxisome proliferator-activated receptors (PPARs) has long been an attractive target for antidiabetic therapy due to the role of PPARs in glycemic control and lipid metabolism. PPAR-α agonists such as rosiglitazone and pioglitazone are used in clinical practice for the treatment of diabetes, and there is some evidence that pioglitazone may have positive effects on cardiovascular complications by virtue of its favorable effects on lipid profiles. However, they have not been shown to reduce macrovascular events. PPAR-α agonism is the mechanism of action in the fibrate class of medications; these agents have bee...Continue Reading

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